Bis-1-benzyl-tetrahydroisoquinolines, generally represented by the structure ##STR6## are an art-recognized class of compounds. In the above formula, X typically represents hydrogen or lower alkoxy, such as methoxy, and R is hydrogen, lower alkoxy or lower alkyl. In certain instances, the nitrogen can be a quaternary nitrogen.
The linking structure represented by "Bridge" in the above formula can be a methylene link as in the early muscle relaxant laudexium which has the structure ##STR7##
In later compounds of this group, the bridge is, in general, a carbon-oxygen structure which typically contains ester linkages. In Taylor et al, U.S. Pat. No. 3,004,031, issued Oct. 10, 1961, the bridge is --(CH.sub.2).sub.m --O.CO--(CH.sub.2).sub.n --CO.O--(CH.sub.2).sub.m -- wherein m is 2 or 3, and n is 0-4. El-Sayad et al, U.S. Pat. No. 4,701,460, issued Oct. 20, 1987, disclose a similar bridge wherein m is 3 and n is 2. The structure of the commercial muscle relaxant atracurium is as given above for laudexium with the exception that the bridge is ##STR8## In Stenlake et al, U.S. Pat. No. 4,179,507, issued Dec. 18, 1979, the bridge is defined as A.CO.O.L.O.CO.B--, wherein A and B are 1-3 carbon alkylene chains, L is a 2-12 carbon alkylene chain or --R--O--R-- where each R has at least two carbon atoms, and their total does not exceed 11 carbon atoms.
Savarese et al, U.S. Pat. Nos. 4,192,877, issued Mar. 11, 1980 and 4,235,906, issued Nov. 25, 1980, disclose compounds of the above general formula wherein the bridge is ##STR9## B and C or either ortho or para and are ##STR10## respectfully, with W being --CH.sub.2 -- or CH.dbd.CH--. Swaringen, Jr. et al, U.S. Pat. No. 4,761,418, issued Aug. 2, 1988, disclose compounds of the above formula wherein the bridge is ##STR11## The compounds described in the above-referenced patents are, in general, neuromuscular blocking agents which produce skeletal muscle relaxation in mammals, including man.
Certain compounds belonging to a second art-recognized group have been found to possess muscle relaxing activity. These are linear tri-, tetra-, penta- and hexa-onium compounds such as those represented by the formulae ##STR12## wherein R and R' are alkyl groups and may be the same or different, m and n are generally 1 to 3, and An.sup.- represents an anion.
There had been over the years a quest for skeletal muscle relaxants of ever-increasing potency. This was based primarily on the philosophy that it is advantageous to use smaller and smaller quantities of a compound to elicit a given therapeutic response since the incidence or severity of side effects would be correspondingly reduced. More recently, however, it has been realized that increases in potency were usually accompanied by delays in onset of activity and duration of activity once begun. Accordingly, what is sought are compounds having a balance of properties, i.e. adequate potency in combination with a rapid onset of activity, comparatively short duration of activity, a good recovery, and an advantageous cardiovascular picture. Such compounds are provided in accordance with the present invention.